The role of leukocytes in renal tissue destruction which occurs in E. coli induced acute pyelonephritis has been investigated Acute pyelonephritis was produced by E. coli in the rats that were treated with cobra venom factor. The cobra venom factor was used to inhibit the generation of complement mediated chemotactic factors and to suppress emigration of leukocytes into the kidney. The suppression of leukocytic emigration into the kidney appears to reduce renal tissue damage of E. coli infected kidneys at least in the very early phase of the disease. In addition, acute pyelonephritis was produced by E. coli in the rats whose leukocytes were depleted in number by administration of nitrogen mustard. The structure of epithelia and basement membrane of tubules was much better preserved in E. coli infected kidneys of leukocyte depleted rats than that of leukocyte nondepleted rats at least in the early phase of the disease. These results indicate that leukocytes play a role in renal tissue destruction. In the future experiment, the leukocytic proteolytic enzymes will be inhibited through the use of inhibitors to find out the role of these enzymes in renal tissue destruction.